共查询到20条相似文献,搜索用时 46 毫秒
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《现代生物医学进展》2012,(22):I0002-I0002
浙江大学医学院免疫学研究所教授鲁林荣带领的研究团队在T淋巴细胞中,发现并命名了一个名叫Tespal的新基因。并阐释了其作用机制,相关论文近日在线发表于国际期刊《自然一免疫学》(Nature Immunology)上。 相似文献
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p53蛋白来源于各种种系的动物,它们有共同的特征,划分为3个不同区域,具有5个高度保守的结构域,每一区域有不同的结构特征和功能,从而使p53发挥诸多的生物学作用 相似文献
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李载平 《中国生物工程杂志》1989,9(2):1-2
一、反向生物学--基因工程的最大冲击波。十几年之前,基因工程出现,生物的基因物质--DNA在化学物质上十分相似,因而基因的纯化,鉴定、结构与功能的研究,曾经为此长期处于困境。 相似文献
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激光对机体免疫功能的影响黄瑜峰,黄卓正广西医科大学附属肿瘤医院530021近十年多来激光技术在临床医学上的应用日益广泛,弱激光照射治疗某些疾病国内外均有许多成功的报道,但对其作用机理目前尚未十分清楚。为此,促使人们探讨弱激光治疗的作用机制进行了多方面... 相似文献
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Sascha Gutmann Alexandra Hinniger Gabriele Fendrich Peter Drückes Sylvie Antz Henri Mattes Henrik M?bitz Silvio Ofner Niko Schmiedeberg Aleksandar Stojanovic Sebastien Rieffel André Strauss Thomas Troxler Ralf Glatthar Helmut Sparrer 《The Journal of biological chemistry》2015,290(24):15210-15218
Macrophages are important cellular effectors in innate immune responses and play a major role in autoimmune diseases such as rheumatoid arthritis. Cancer Osaka thyroid (COT) kinase, also known as mitogen-activated protein kinase kinase kinase 8 (MAP3K8) and tumor progression locus 2 (Tpl-2), is a serine-threonine (ST) kinase and is a key regulator in the production of pro-inflammatory cytokines in macrophages. Due to its pivotal role in immune biology, COT kinase has been identified as an attractive target for pharmaceutical research that is directed at the discovery of orally available, selective, and potent inhibitors for the treatment of autoimmune disorders and cancer. The production of monomeric, recombinant COT kinase has proven to be very difficult, and issues with solubility and stability of the enzyme have hampered the discovery and optimization of potent and selective inhibitors. We developed a protocol for the production of recombinant human COT kinase that yields pure and highly active enzyme in sufficient yields for biochemical and structural studies. The quality of the enzyme allowed us to establish a robust in vitro phosphorylation assay for the efficient biochemical characterization of COT kinase inhibitors and to determine the x-ray co-crystal structures of the COT kinase domain in complex with two ATP-binding site inhibitors. The structures presented in this study reveal two distinct ligand binding modes and a unique kinase domain architecture that has not been observed previously. The structurally versatile active site significantly impacts the design of potent, low molecular weight COT kinase inhibitors. 相似文献
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Ben Moree Guowei Yin Diana F. Lázaro Francesca Munari Timo Stroh?ker Karin Giller Stefan Becker Tiago F. Outeiro Markus Zweckstetter Joshua Salafsky 《The Journal of biological chemistry》2015,290(46):27582-27593
Proteins are structurally dynamic molecules that perform specialized functions through unique conformational changes accessible in physiological environments. An ability to specifically and selectively control protein function via conformational modulation is an important goal for development of novel therapeutics and studies of protein mechanism in biological networks and disease. Here we applied a second-harmonic generation-based technique for studying protein conformation in solution and in real time to the intrinsically disordered, Parkinson disease related protein α-synuclein. From a fragment library, we identified small molecule modulators that bind to monomeric α-synuclein in vitro and significantly reduce α-synuclein aggregation in a neuronal cell culture model. Our results indicate that the conformation of α-synuclein is linked to the aggregation of protein in cells. They also provide support for a therapeutic strategy of targeting specific conformations of the protein to suppress or control its aggregation. 相似文献
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David W. Banner Bernard Gsell Jrg Benz Julian Bertschinger Dominique Burger Simon Brack Simon Cuppuleri Maja Debulpaep Alain Gast Dragan Grabulovski Michael Hennig Hans Hilpert Walter Huber Andreas Kuglstatter Eric Kusznir Toon Laeremans Hugues Matile Christian Miscenic Arne C. Rufer Daniel Schlatter Jan Steyaert Martine Stihle Ralf Thoma Martin Weber Armin Ruf 《Acta Crystallographica. Section D, Structural Biology》2013,69(6):1124-1137
The aspartic protease BACE2 is responsible for the shedding of the transmembrane protein Tmem27 from the surface of pancreatic β‐cells, which leads to inactivation of the β‐cell proliferating activity of Tmem27. This role of BACE2 in the control of β‐cell maintenance suggests BACE2 as a drug target for diabetes. Inhibition of BACE2 has recently been shown to lead to improved control of glucose homeostasis and to increased insulin levels in insulin‐resistant mice. BACE2 has 52% sequence identity to the well studied Alzheimer's disease target enzyme β‐secretase (BACE1). High‐resolution BACE2 structures would contribute significantly to the investigation of this enzyme as either a drug target or anti‐target. Surface mutagenesis, BACE2‐binding antibody Fab fragments, single‐domain camelid antibody VHH fragments (Xaperones) and Fyn‐kinase‐derived SH3 domains (Fynomers) were used as crystallization helpers to obtain the first high‐resolution structures of BACE2. Eight crystal structures in six different packing environments define an ensemble of low‐energy conformations available to the enzyme. Here, the different strategies used for raising and selecting BACE2 binders for cocrystallization are described and the crystallization success, crystal quality and the time and resources needed to obtain suitable crystals are compared. 相似文献
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Expressed Sequence Tags (ESTs) are short, usually unedited sequences obtained by single-pass sequencing of cDNA clones from
any cDNA library. Analyzing and comparing ESTs can provide information on gene expression, function and evolution. Large-scale
EST sequencing has become an attractive alternative to plant genome sequencing. Currently, plant EST collections comprise
over 3.8 million sequences from about 200 species. They have proved to be a valuable tool for gene discovery and plant metabolism
analysis. Several plant-specific EST databases have been created which provide access to sequence data and bioinformatics-based
tools for data mining. Searching EST collections allows pre-selection of genes for preparing cDNA arrays, targeted to bring
maximum information on specialized processes, like stress response, symbiotic nitrogen fixation etc. Also, ESt-based molecular
markers such as SNP, SSR, and indels are fast developing tools for breeders and researchers. 相似文献
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Current drug discovery efforts generally focus on a limited number of protein classes, typically including proteins with well-defined catalytic active sites (e.g., kinases) or ligand binding sites (e.g., G protein-coupled receptors). Nevertheless, many clinically important pathways are mediated by proteins with no such obvious targets for small molecule inhibitors. Allosteric inhibitors offer an alternative approach to inhibition of protein activities, particularly for proteins that undergo conformational changes as part of their activity cycle. Proteins regulated by autoinhibitory domains represent one broad class of proteins that meets this criterion. In this article, we discuss the potential of autoinhibited proteins as targets for allosteric inhibitors and describe two examples of small molecules that act by stabilizing native autoinhibited conformations of their targets. We propose that proteins regulated by autoinhibition may be generally amenable to allosteric inhibition by small molecules that stabilize the native, autoinhibited fold. 相似文献
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Walke DW Han C Shaw J Wann E Zambrowicz B Sands A 《Current opinion in biotechnology》2001,12(6):626-631
A vast number of genes of unknown function threaten to clog drug discovery pipelines. To develop therapeutic products from novel genomic targets, it will be necessary to correlate biology with gene sequence information. Industrialized mouse reverse genetics is being used to determine gene function in the context of mammalian physiology and to identify the best targets for drug development. 相似文献